1. Field of the Invention
The present invention relates to the use of 2,3-dihydroxyterephthalamides as highly efficient monomeric metal ion chelating agents to sequester metal ions in aqueous solutions. More specifically, it is the use of these compounds to sequester iron ions in aqueous solutions such as mine drainage, industrial waste water, foods or human or mammalian blood or plasma.
2. Description of Related Art
The most powerful of the siderophores is enterobactin (log K.sub.f equal to about 52, see W. R. Harris, et al. (1979) below) which contains three 2,3 dihydroxy-benzamide binding subunits (such as subunit type A in FIG. 1) which is pendant from a tri-serine backbone.
ArtAd of interest in this chelate technology includes:
D. F. Busch, et al. (1971), Advanced Chemical Ser., Vol. 100, p. 44.
D. H. Cabiness, et al., (1969), Journal of the America Chemical Society, Vol. 91, pp. 6540-6541.
W. R. Harris, et al. (1979), Journal of the American Chemical Society. Vol. 101, pp. 6097-6104.
J. -M. Lehn, (1985) Science, Vol. 227, pp. 849-856.
L. D. Loomis, (1986), Ph. D. Dissertation University of California, Berkeley, Ca.
T. J. McMurry, et al. (1987), Journal of the American Chemical Society, Vol. 109, pp. 3451-3453.
T. J. McMurry, et al. (1987A), Journal of the American Chemical Society, Vol. 109, pp. 7196-7198.
A. E. Martell, (1981), "Development of Iron Chelators for Clinical Use." New York, N.Y.: Elsevier North Holland Inc. pp. 67-104.
A. E. Martell, et al. (1976), Critical Stabilitv Constants, Plenum: New York, N.Y.: Vol IV, p.1.
K. N. Raymond, et al. (1984), Topics in Current Chemistry, Vol. 123, pp. 50-102.
S. J. Rogers, et al. (1985), Journal of the American Chemical Society, Vol. 107 pp. 4094-4095.
K. N. Raymond, et al. (1988), Pure and Applied Chemistry, Vol. 60, No. 4, pp. 545-548.
R. C. Scarrow, (1985), Ph.D. Dissertation University of California at Berkeley.
R. C. Scarrow, et al. (1988), Inorganic Chemistry, Vol. 27, pp. 4140-4149.
H. Stunzi, et al. (1979), Australian Journal of Chemistry, Vol. 32, pp. 21-30.
H. Stunzi, et al. (1980), Australian Journal of Chemistry, Vol. 33, pp. 2207-2220.
P. Statte, et al. (1987). Tetrahedron, Vol. 43, pp. 2065-2074.
Y. Sun, et al. (1986), Inorganic Chemistry, Vol. 25, p. 4780.
F. L. Weitl, et al. (1981), Journal of Medicinal Chemistry, Vol. 24, pp. 203-206.
K. Wolgang, et al. (1984), Angewante Chemie International. Ed.-English, Vol. 23, p. 714.
All of the articles, patents and references cited in this application are incorporated herein by reference.
Recently, a number of reports (e.g., K. Wolgang, et al. (1984); P. Sutte, et al., (1987); Y. Sun, et al. (1986); S. J. Rogers, et al., (1985); T. J. McMurry, et al. (1987) and (1987A)) describe the production of macrobi-cycles such as compound #12 and compound #13 and macrocycles such as compound #14 (shown in FIG. 2) which are not based on the 2, 3-dihydroxybenzamide moiety found in enterobactin. Instead these polycyclic compounds are based on the 2,3-dihydroxyterephthalamide, structure B (FIG. 1 ), as the binding subunit.
A number of reports, e.g. D. K. Cabbiness, et al. (1969); D. H. Busch, et al., (1971); J.-M. Lehn and A. E. Martell (1981), use the term "macrocyclic effect" to describe the increased stability gained by a chelating agent when all binding subunits are incorporated into a macrocycle or macrobicycle.
In a strategy toward a more effective chelating agent, the enthalpic properties of the new binding subunit have not been heretofore considered or appreciated. It is therefore useful and desirable to recognize that monomeric 2,3-dihydroxyterephthalamides have remarkably high binding constants for metal atoms in aqueous solution. The present invention accomplishes that objective.